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Copper transport drug restores memory and clears toxic Alzheimer's proteins

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Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#61

Post by wk_end »

bluGill wrote: post #49
mimicmagnet wrote: post #35

Earlier quoted context omitted.

https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.

It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.

In general, sure, but in this specific instance (treating Alzheimer's by clearing amyloid-beta) it's been shown over and over again to not work in humans.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#62

Post by DavidSJ »

dekhn wrote: post #60
DavidSJ wrote: post #56

Earlier quoted context omitted.

Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined. If your view is merely that there is a "camp" of experts that disagrees, then sure, but in that case, I do not think it is honest to frame this as a choice between believing in the authority of a single exp…

My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature (the entire amyloid establishment isn't going to give up its dominant position easily). Also, I didn't say anything about the evidence (I don't have a "read" on the evidence, because I don't read Alz literature). My point is entirely that my priors indicate that Derek is a…

You said the camp promoting the amyloid hypothesis has struggled greatly to come up with evidence to support its position. What did you mean by that if not a read of the quality of the evidence?

Why do you continue to frame this as a choice between a single cherry-picked expert's opinion, and my own non-expert opinion? Either fairly represent the spectrum of experts' views, or decide based on the actual evidence and arguments.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#63

Post by john_strinlai »

dekhn wrote: post #60
DavidSJ wrote: post #56

Earlier quoted context omitted.

Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined. If your view is merely that there is a "camp" of experts that disagrees, then sure, but in that case, I do not think it is honest to frame this as a choice between believing in the authority of a single exp…

My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature (the entire amyloid establishment isn't going to give up its dominant position easily). Also, I didn't say anything about the evidence (I don't have a "read" on the evidence, because I don't read Alz literature). My point is entirely that my priors indicate that Derek is a…

>My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature

>I don't have a "read" on the evidence, because I don't read Alz literature

these two sentences seem contradictory to me. i am not sure how you would keep up on the research (to know it's moved from majority-held to minority-held view), and know that the move is not reflected in the literature, without reading the literature.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#64

Post by dekhn »

DavidSJ wrote: post #62
dekhn wrote: post #60

Earlier quoted context omitted.

My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature (the entire amyloid establishment isn't going to give up its dominant position easily). Also, I didn't say anything about the evidence (I don't have a "read" on the evidence, because I don't read Alz literature). My point is entirely that my priors indicate that Derek is a…

You said the camp promoting the amyloid hypothesis has struggled greatly to come up with evidence to support its position. What did you mean by that if not a read of the quality of the evidence? Why do you continue to frame this as a choice between a single cherry-picked expert's opinion, and my own non-expert opinion? Either fairly represent the spectrum of experts' views, or decide based on the actual evidence and…

My estimate of the quality of the evidence is based on daily discussions with people who work in that field and reading summary articles in major journals. I typically don't read raw scientific articles directly- those are aimed at people in the field. Instead, my understanding comes from a synthesis of expert opinions weighted by my own priors (based on 30+ years in the field). Derek's opinion is now the prevailing one that I hear from a wide range of researchers.

I've seen this happen before, btw- overturning establishment paradigms, especially ones where the underlying etiology is complex- is extremely hard and often takes decades of experimental results.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#65

Post by dekhn »

john_strinlai wrote: post #63
dekhn wrote: post #60

Earlier quoted context omitted.

My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature (the entire amyloid establishment isn't going to give up its dominant position easily). Also, I didn't say anything about the evidence (I don't have a "read" on the evidence, because I don't read Alz literature). My point is entirely that my priors indicate that Derek is a…

> My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature > I don't have a "read" on the evidence, because I don't read Alz literature these two sentences seem contradictory to me. i am not sure how you would keep up on the research (to know it's moved from majority-held to minority-held view), and know that the move is not ref…

Most scientists who are not experts in their field don't read the literature for a field directly. Instead, they synthesize their opinions about the field by consulting experts, and weighing various sorts of evidence. In my case, I work in an adjacent field and see presentations from scientists, have casual conversations with them, and read the news articles in major journals.

The raw literature for alzheimer's, as well as biomed in general, is not really easily interpretable. It's rife with errors, misleading statements, and intentional obfuscation.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#66

Post by avgDev »

nphardon wrote: post #46
avgDev wrote: post #19

My mother has early onset alzheimer's disease. We currently know very little about the disease and the current treatment options are controversial. The efficacy of the medications removing the amyloid plaque from the brain is questionable, as people still decline. What makes alzheimer's difficult is that it is not really a single uniform disease. There are subtypes. Since my mother has it, I was presented with an opt…

How old is your mother? Iirc PSEN1 correlates to very early AD, like late 30s early 40s. My dad had full blown AD at 65, with serious cognitive decline starting at 63, and that felt very early to us all. My dad had no AD biomarkers on full genetic scan. My heart goes out to you and your family.

She is now 63. Started showing symptoms at 61. Her sister died at 64 and her onset was in her 50s.

I am working with invitae to get her DNA tested. Unfortunately, her stage is considered moderate and very little treatment options.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#67

Post by tremon »

bluGill wrote: post #6
quadhome wrote: post #5

Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. In the words of Derek Lowe: Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-f…

I care what works, not about debate. This seems to work and that trumps any debate about what the real means are. Don't get me wrong, if you are in this area of research this debate is important. There may be other types of Alzheimer's that have a different means. This drug may actually target something else. There might be some other truth I haven't thought it - but to me as an outsider the important part is a treat…

> to me as an outsider the important part is a treatment that works, not why it works

Are you a mouse, perhaps? We have a plethora of treatments for mice suffering from human-induced Alzheimer's. None of those treatments have ever been shown to work for human patients, and this one is no different.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#68

Post by avgDev »

dbcurtis wrote: post #14
quadhome wrote: post #5

Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. In the words of Derek Lowe: Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-f…

> Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. Isn't the current thinking that amyloid-beta buildup is a marker, not a cause? The therapy may be working here, but it isn't clear whether clearing amyloid-beta proteins is the mechanism or an outcome.

From what I read your statement is accurate. From speaking to people who are going through the new infusions Leqembi and Kisunla get rid of amyloid plaque doesn't mean the decline stops, and if the disease was driven by it then it would stop.

Also, studies show some slowing using these new drugs, but the disease still progresses. Therefore, the plaque is most likely a symptom. It could be the driver in some of the cases though, I think in genetic PSEN1 alzheimer's. I've read a paper discussing issue with the body not removing it and allowing to build up.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#69

Post by DavidSJ »

dekhn wrote: post #64
DavidSJ wrote: post #62

Earlier quoted context omitted.

You said the camp promoting the amyloid hypothesis has struggled greatly to come up with evidence to support its position. What did you mean by that if not a read of the quality of the evidence? Why do you continue to frame this as a choice between a single cherry-picked expert's opinion, and my own non-expert opinion? Either fairly represent the spectrum of experts' views, or decide based on the actual evidence and…

My estimate of the quality of the evidence is based on daily discussions with people who work in that field and reading summary articles in major journals. I typically don't read raw scientific articles directly- those are aimed at people in the field. Instead, my understanding comes from a synthesis of expert opinions weighted by my own priors (based on 30+ years in the field). Derek's opinion is now the prevailing…

What started as an argument to ignore arguments and evidence and instead rely on authority, seems now to have morphed into an argument that we should ignore the authority of the establishment, because of your own personal assessment of the evidence (which you have not yourself read) and your own personal synthesis of conversations you've had with researchers you've personally come into contact with (despite this being apparently unrepresentative of objective measures of typical researcher opinions).

Arguing from authority really only takes you so far when it ends up as an appeal to your personal experience. I'd rather you either address the arguments directly, or drop the dubious appeal to authority.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#70

Post by bijowo1676 »

avgDev wrote: post #68
dbcurtis wrote: post #14

Earlier quoted context omitted.

> Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. Isn't the current thinking that amyloid-beta buildup is a marker, not a cause? The therapy may be working here, but it isn't clear whether clearing amyloid-beta proteins is the mechanism or an outcome.

From what I read your statement is accurate. From speaking to people who are going through the new infusions Leqembi and Kisunla get rid of amyloid plaque doesn't mean the decline stops, and if the disease was driven by it then it would stop. Also, studies show some slowing using these new drugs, but the disease still progresses. Therefore, the plaque is most likely a symptom. It could be the driver in some of the ca…

I read it somewhere that amyloid plaques were actually defensive mechanism of the body to counter the damage to brain from disease, so removing the plagues makes things worse for patients

https://www.salk.edu/news-release/in-surprising-twist-some-a...

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